Oral Topotecan to Treat Recurrent or Persistent Solid Tumors

• The secondary endpoints are: the tolerability profile [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
• response rates [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
• pharmacokinetic parameters [ Time Frame: Weekly ] [ Designated as safety issue: No ]
• biomarker evaluations (TSP-1, CEPC, VEGF, Topo-1, HIF-1, CD31 vessel counts) [ Time Frame: Every 4-8 weeks depending on the biomarker ] [ Designated as safety issue: No ]
• and tumor marker responses. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the effectiveness of oral topotecan and how well the chemotherapy is tolerated (any side effects) when it is given in different dose levels. The study will also collect information on how the medication is being broken down and absorbed in the body and how quality of life is affected during treatment.

Inclusion Criteria:

• Patient provides written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• Male or female patients.
• Patient is at least 18 years of age with recurrent or persistent solid tumors.
• Patient has adequate hematologic function (absolute neutrophil count [ANC] >= 1500/mL and platelets >= 100,000/mL), adequate renal function (serum creatinine < 2.0 mg/dL; calculated creatinine clearance > 40 mL/min), and adequate hepatic function (serum bilirubin <= 1.5 mg/dL and transaminases <= 3 times the upper limit of normal [3 x ULN]).
• Patient has Eastern Oncology Cooperative Group (ECOG) performance status of <= 2.
• Patient has a life expectancy of at least 3 months at time of enrollment.
• Patient has no medical problems, unrelated to the malignancy, of sufficient severity which would limit full compliance with the study or which would expose him/her to undue risks.
• Patient has received no more than 2 prior treatment regimens prior to enrollment including chemotherapy, hormonal therapy, biologic therapy, and immunotherapy.
• Patient has a negative serum or urine pregnancy test within 7 days prior to starting therapy (if a female of childbearing potential).

Exclusion Criteria:

• Patient is a pregnant or lactating woman. Women of childbearing potential with either a positive or no pregnant test (serum or urine) at baseline. Women of childbearing potential not using a reliable and appropriate contraceptive method will be excluded. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.) Patients must agree to continue contraception for 30 days from the date of the last study drug administration.
• Patient has serious, uncontrolled, concurrent infection(s).
• Patient has received whole pelvic or extended field radiation therapy within 4 weeks of enrollment. Patients who have not fully recovered or whose acute toxicity related to prior radiotherapy has not returned to baseline are ineligible.
• Patient has received myelosuppressive chemotherapy within the last 4 weeks or has not recovered from the myelosuppressive effects of recent chemotherapy.
• Patient has received another investigational agent within 4 weeks prior to study enrollment.
• Patient has known hypersensitivity to topoisomerase I inhibitors.
• Patient is unable to swallow a capsule or has a disease known to affect drug absorption, such as short gut syndrome or active radiation enteritis.
• Patient has received drugs known to alter absorption such as antacids, proton pump blockers (eg, omeprazole), or H2 receptor antagonists (eg, cimetidine). A washout period of one week (7 days) is required prior to initiating study medication.